5-FUrd rescues axonopathy induced by co-expressing human SOD1 and WT TDP-43 in zebrafish. When human SOD1 and TDP-43 are co-expressed in zebrafish (A, exemplar cross-sections of spinal cord), the motor neurons exhibit axonopathy (B and C), and this axonopathy can be partially but significantly rescued with drugs that block human SOD1 Trp32. Scale bar represents 200 μm. B, 5-fluorouridine (5-FUrd, 1.5 μM) rescued axonopathy in embryos injected with SOD1 and WT TDP-43 (p = 0.011). C, a significant reduction was also observed with 5-FUrd in SOD1 and TDP-43ΔNLS-injected embryos (p = 0.040). Both vehicle and 5-FUrd solutions contained 5 μM uridine and 0.2% DMSO. Error bars indicate SEM; ∗p < 0.05 (Mann-Whitney pairwise comparisons); sample sizes are noted at the base of each bar. SOD1, superoxide dismutase; TDP, TAR DNA-binding protein.
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